Electroactive injectable hydrogel based on oxidized sodium alginate and carboxymethyl chitosan for wound healing.

Electroactive hydrogel is of great significance in restoring wound currents, promoting cell proliferation, and accelerating the wound healing process. However, the poor dispersity and underlying toxicity of electronic conductive fillers and high concentration of ionic conductors in traditional electroactive hydrogel limited its application in medical care. Herein, an electroactive oxidized sodium alginate/carboxymethyl chitosan/silver nanoparticles (OSA/CMCS/AgNPs) hydrogel was constructed with no additional conductive fillers or synthesized conductive polymers being added, in which the dynamic imine bonds were rapidly formed between aldehyde groups in OSA and amino groups in CMCS, and AgNPs were further in situ formed by UV irradiation. The electroactive hydrogel exhibited the injectable property, strong self-healing ability, excellent biocompatibility, and high antibacterial activities. Moreover, the electroactive hydrogel can significantly promote the proliferation of L929 cells under electrical stimulation. Furthermore, the electroactive hydrogel was proved to significantly accelerate the wound healing process in the full-thickness skin defect model, exhibiting anti-inflammation, promoting the fibroblasts proliferation, angiogenesis, and collagen deposition under electrical stimulation. In summary, the current work explored a novel strategy to construct the polysaccharides-based electroactive hydrogel with good biocompatibility and multi-functions, which is promising to be used in deep wound treatment.

Preparation of zinc phthalocyanine-loaded amphiphilic phosphonium chitosan nanomicelles for enhancement of photodynamic therapy efficacy.

To increase the solubility and the encapsulation of zinc phthalocyanine (ZnPc) photosensitizer for photodynamic therapy (PDT), a positively charged amphiphilic phosphonium chitosan nanomicelle with multi-benzene structure was developed, and its application to PDT was explored. N-acetyl-l-phenylalanine-(4-carboxybutyl) triphenylphosphonium bromide chitosan (CTPB-CS-NAP), a chitosan derivative with tunable amphiphilicity, was synthesized first. ZnPc was encapsulated in CTPB-CS-NAP at the critical micelle concentration (CMC) of 4.898 mg/L by a hydrophobic self-assembly method to form ZnPc-loaded nanomicelles (ZnPc@CTPB-CS-NAP). The method gives the highest encapsulation efficiency and drug loading of 89.4 % and 22.3 %, respectively. ZnPc@CTPB-CS-NAP is stably dispersed in aqueous solution and shows the average particle size of 103±5 nm. PDT experiments suggest the phototoxicity of ZnPc@CTPB-CS-NAP is much higher than that of ZnPc, but no obvious dark cytotoxicity is observed. Our study has provided a new strategy for improving the photodynamic therapy efficacy of hydrophobic photosensitizer by the encapsulation with chitosan derivative carriers.

Construction of pH/glutathione responsive chitosan nanoparticles by a self-assembly/self-crosslinking method for photodynamic therapy.

A novel pH/glutathione (GSH) multi-responsive chitosan nanoparticles (NPs) material has been successfully designed and prepared by a self-assembly/self-crosslinking method for photodynamic therapy (PDT), which overcomes the shortcomings of traditional photosensitizer carriers, such as poor chemical stability, low loading efficiency and single-responsive photosensitizer release. Amphiphilic sulfhydryl chitosan (SA-CS-NAC) is first prepared by modifying chitosan (CS) with stearic acid (SA) and N-acetyl-L-cysteine (NAC), and then subject to self-assembly and self-crosslinking in the presence of photosensitizer, indocyanine green (ICG), to form the ICG-loaded amphiphilic sulfhydryl chitosan nanoparticles (SA-CS-NAC@ICG NPs). The ICG entrapment efficiency and loading efficiency of the NPs are found to be 95.2% and 27.6%, respectively. The multi-responsive ICG release of the NPs to the low pH and high GSH content of the microenvironment in tumor cells is successfully achieved. Under the laser irradiation, the SA-CS-NAC@ICG NPs produce the amount of reactive oxygen species (ROS) twice of that generated by free ICG under the same conditions. The in vitro cell experiment confirmed the strong cellular uptake ability, low biotoxicity and good tumor inhibition of the NPs. Our work has provided a new strategy for the targeted photosensitizer delivery for PDT.

Effects of salt concentration on the structure and properties of composite fiber of carboxymethyl cellulose/N-2-hydroxylpropyl trimethyl ammonium chloride chitosan prepared by polyelectoyte complexation-freeze drying.

The conventional electrospinning process for the preparation of fibers usually require complex equipment and complicated preparation processes, as well as chemical crosslinkers and organic solvents, which limits its application in the preparation of biomedical materials. In the current study, carboxymethyl cellulose/N-2-hydroxylpropyl trimethyl ammonium chloride chitosan (CMC/HACC) composite fibers were fabricated by polyelectrolyte complexation (PEC) and freeze drying coupled method in both pure water and NaCl solution. The structures of the as-prepared fibers and the effects of NaCl concentration on the structures of fibers were studied by FTIR, solid 13C NMR, XRD, XPS and SEM. The formation mechanism of the composite fiber and the effects of NaCl concentration on structure and properties of the composite fiber were simulated in the Materials Studio software and discussed. The swelling properties and the thermal decomposition kinetics of the composite fiber were studied. The results suggest that the addition of NaCl electrolyte to the complexing system significantly affects the structure and properties of the PEC fiber. Our work has provided a new preparation route to the composite fibers of natural polymers with controllable structures and properties by the combination of PEC and freeze drying techniques using NaCl with desired concentration as the electrolyte.

Natural Hydrogels Applied in Photodynamic Therapy.

Natural hydrogels are three-dimensional (3D) water-retaining materials with a skeleton consisting of natural polymers, their derivatives or mixtures. Natural hydrogels can provide sustained or controlled drug release and possess some unique properties of natural polymers, such as biodegradability, biocompatibility and some additional functions, such as CD44 targeting of hyaluronic acid. Natural hydrogels can be used with photosensitizers (PSs) in photodynamic therapy (PDT) to increase the range of applications. In the current review, the pertinent design variables are discussed along with a description of the categories of natural hydrogels available for PDT.

Synthesis and application of a series of amphipathic chitosan derivatives and the corresponding magnetic nanoparticle-embedded polymeric micelles.

Magnetic nanoparticle-embedded polymeric micelles (MNP-PMs) prepared with amphipathic polymers are an important sustained-release carrier for hydrophobic drugs. The amphipathic chitosan derivatives (ACDs) based stimuli-responsive slow-release carriers have attracted considerable attentions because of the bioactivities and modifiability of chitosan. In the current study, a series of ACDs including alkylated N-(2-hydroxy) propyl-3-trimethyl ammonium chitosan chloride (alkyl-HTCC) and alkylated polyethylene glycol N-(2-hydroxy) propyl-3-trimethyl ammonium chitosan chloride (alkyl-PEG-HTCC) were prepared by the reductive amination of HTCC and PEG-HTCC, and their structures and properties were characterized. Octyl-HTCC/O-Fe3O4 and octyl-PEG-HTCC/O-Fe3O4 MNP-PMs were prepared by the hydrophobic interactions between the corresponding ACDs and oil soluble Fe3O4 magnetic nanoparticles (O-Fe3O4 MNPs), and characterized for the structure, magnetic performance and surface charge state. Their potential application as a drug delivery carrier was investigated upon the embedding efficiency and pH dependent sustained-release performance using the hydrophobic drug, paclitaxel (PTX), as a model drug. Our work has provided a new application strategy of ACDs in the multi-functional drug delivery carrier.

Preparation of chitosan-Cu2+/NH3 physical hydrogel and its properties.

Chitosan (CTS) physical hydrogels crosslinked under gaseous ammonia atmospheres have attracted considerable attentions for their abilities to maximize the biological activities of CTS while maintaining their biocompatibility. However, poor mechanical properties significantly limit their application. The CTS-metal ion complexing hydrogels showed better mechanical properties. However, the formation process is uncontrollable, and the high dosages of metal ions used may cause cytotoxicity. In the present work, CTS-Cu2+/NH3 physical hydrogel with excellent comprehensive properties was prepared by ammonia fumigation and metal ion complexation. Its formation mechanism and structure were investigated. The above physical hydrogel revealed excellent mechanical properties with the mechanical strength up to 0.30 MPa, significantly higher than CTS/NH3 hydrogel, even at much lower Cu2+ contents. And CTS-Cu2+/NH3 hydrogel is more thermal stable than CTS/NH3 hydrogel. In addition, it exhibited specific killing effects on Pseudomonas aeruginosa. These results suggest that CTS-Cu2+/NH3 physical hydrogel has a great application potential as a wound dressing.